沙利度胺联合抗PD1抗体对增强肺癌治疗免疫力的强化作用

Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy.

作者信息

Liu Qing, Chiang Zu-Chian, Zhao Xiangqian, Cui Dongya, Li Xinxin, Chen Hao, Lin Fangyu, Jiang Tao, Chen Qi, Lin Xiaoyan, Lin Jizhen

机构信息

The Oncology Department of Union Hospital, Fujian Medical University, Fuzhou, Fujian, China.

The Cancer Center, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China.

出版信息

Curr Pharm Biotechnol. 2025 Jan 3. doi: 10.2174/0113892010319495241218114812.

DOI:10.2174/0113892010319495241218114812

PMID:39773053

Abstract

OBJECTIVE

Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.

METHODS

We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.

RESULTS

THD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density.

CONCLUSION

This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

摘要

目的

联合使用免疫检查点抑制剂和抗血管生成药物为对抗免疫检查点和肿瘤内血管生成对实体瘤生长的协同促进作用提供了一种有前景的策略。

方法

我们研究了沙利度胺（THD）和抗PD-1抗体（PD-1 mAb）在抑制肿瘤生长、增强免疫力和抑制血管生成方面的潜力。

结果

THD对CD4+ T细胞中的PD-1和癌细胞中的PD-L1具有调节作用，同时对A549和Lewis肺癌（LLC）细胞系具有肿瘤生长抑制作用。与PD-1 mAb联合使用时，THD增加了CD4+ T细胞中细胞内IL-2和IFN-γ的表达，增强了外周血单个核细胞（PBMC）中颗粒酶（Gzm-B）的表达，并降低了CD4+ T细胞中TNF-α的表达。在C57BL/6小鼠中，THD加PD-1 mAb降低了LLC衍生的肺肿瘤重量和体积，促进了肿瘤中CD8+ T细胞浸润，并降低了肿瘤内CD34+微血管密度。